Using large-scale RNAi screens to identify novel drug targets for cancer.

In recent years, the development and clinical implementation of targeted therapeutics have progressed significantly. The specific inhibition of components of signal transduction pathways controlling proliferation and survival has been a highly successful research strategy. However, cancer is a heterogeneous disease and, even within one type of cancer, different genetic alterations are associated with identical phenotypes. To advance the use of targeted therapeutics, it is not only essential to identify the crucial factors in the signal transduction networks that control cell proliferation and survival, but also to classify individual tumors according to genetic alterations that correlate with pathway activation. RNAi screening technologies have become established as an important strategy both to identify novel targets and to provide novel biomarkers that are crucial for the further development of personalized medicine. This feature review discusses different RNAi screening strategies and their contribution to the rapidly evolving field of targeted therapeutics.